Despite successful control of viremia by combined antiretroviral therapy, brain infection and its resulting neurocognitive impairment remain a prevalent comorbidity in HIV infected individuals. HIV invades the brain early in the course of infection via penetration through the blood-brain barrier (BBB). While the impact of HIV on BBB astrocytes and endothelial cells is relatively well studied, the role of pericytes in BBB regulation during HIV infection remains unclear; however, it is known that a selective population of pericytes is prone to infection. In the present study, we hypothesize that injury signals are propagated from infected pericytes to neighboring cells via gap junction (GJ)-mediated intercellular communication. Among a variety of studied GJ proteins, HIV infection of human brain pericytes specifically increased expression of connexin 43 as determined by immunoblotting and immunostaining. This effect was confirmed in the brains of mice infected with EcoHIV, a mouse-specific HIV strain. In addition, HIV infection enhanced functional GJ-mediated intercellular communication in pericytes. The importance of this process was confirmed in experiments in which inhibition of GJs by carbenoxolone attenuated HIV infection. In addition to GJs, an extracellular ATP release assay revealed that HIV may also play a role in opening of connexin (Cx)-containing hemichannels (HCs). Overall, these findings indicate an important role of GJs in the propagation of HIV infection in human brain pericytes that may contribute to BBB dysfunction in brain infection and the pathogenesis of NeuroAIDS.
Evidence from 7 of the 11 included studies suggests significant improvement in patients' hemoglobin A1c (HbA1c) with the use of secure messaging. However, improvements in patients' secondary outcomes, such as blood pressure and cholesterol, were inconsistent. Further work must be done to determine how to best maximize the potential of available tools such as secure messaging and EHRs to improve patient outcomes.
Immune checkpoint blockade (ICB) improves survival in many types of cancers including melanoma, non-small cell lung, renal cell, breast, and cervical cancers. However, many of these therapies are also associated with high grade dermatologic adverse events (DAEs), including Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), SJS/TEN-like reactions, high grade maculopapular and psoriasiform rashes, autoimmune bullous eruptions, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may limit their tolerability and use. It is important to properly identify and treat DAEs to ICB because these DAEs may be associated with positive anti-tumor response and patients may have limited options for alternative anti-cancer therapeutics. In this review, we describe high grade DAEs to increasingly used ICB agents, which target CTLA-4 and PD-1 or its ligand, PD-L1 and enable the immune system to target cancer cells. We further differentiate life-threatening adverse reactions from mimickers and report cases of serious DAEs which have been recorded in association with ICB through the FDA Adverse Events Reporting System (FAERS), which is an archive of adverse events associated with various drugs and therapeutic biologic products reported voluntarily by consumers and healthcare professionals as well as mandatorily by manufacturers. Lastly, we summarize management recommendations for these adverse events and discuss knowledge and evidence gaps in this area.
Health disparities encompass a wide range of personal, societal, environmental, and system-based factors that contribute to inequitable health and health outcomes in vulnerable patient populations.These factors interact with the biologic and genetic elements of disease, becoming difficult to isolate when researching disease and outcomes. However, addressing the non-biologic determinants of health that contribute to patient outcomes is integral to practicing effective and equitable medicine.
Background: The rising prevalence of allergies can substantially impact the skin, which is one of the largest targets for allergic and immunologic responses. Objective: Here, we describe the results of an online survey assessing self-reported allergy prevalence in Americans, outline the populations who report allergies, and characterize the skin conditions associated with allergy. Methods: An online survey was conducted in the USA of 2008 adults as a representative sample of the general American population. Results: 41.7% of American adults (mean age 44.7 ± 15.3 years old) reported having allergies. Reported allergies included respiratory allergies (45.2%), skin allergies (41.4) and food allergies (33.9%). 47.7% of those who reported allergies also reported experiencing associated skin reactions. In addition, those who reported allergies were 2 to 4.5 times more likely to report a cutaneous skin disease, 7 times more likely to report sensitive skin, and twice as likely to report experiencing skin reactions when using skincare products compared to those who did not report allergies. Conclusions: It is estimated that over 100 million American adults have allergies. These results will help raise awareness about the burden of allergies and the need to develop solutions to mitigate their impact on health.
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